Surveillance of HIV-1 pol transmitted drug resistance in acutely and recently infected antiretroviral drug-naïve persons in rural western Kenya

Abstract

HIV-1 transmitted drug resistance (TDR) is of increasing public health concern in sub-Saharan Africa with the rollout of antiretroviral (ARV) therapy. Such data are, however, limited in Kenya, where HIV-1 drug resistance testing is not routinely performed. From a population-based household survey conducted between September and November 2012 in rural western Kenya, we retrospectively assessed HIV-1 TDR baseline rates, its determinants, and genetic diversity among drug-naïve persons aged 15-59 years with acute HIV-1 infections (AHI) and recent HIV-1 infections (RHI) as determined by nucleic acid amplification test and both Limiting Antigen and BioRad avidity immunoassays, respectively. HIV-1 pol sequences were scored for drug resistance mutations using Stanford HIVdb and WHO 2009 mutation guidelines. HIV-1 subtyping was computed in MEGA6. Eighty seven (93.5%) of the eligible samples were successfully sequenced. Of these, 8 had at least one TDR mutation, resulting in a TDR prevalence of 9.2% (95% CI 4.7-17.1). No TDR was observed among persons with AHI (n = 7). TDR prevalence was 4.6% (95% CI 1.8-11.2) for nucleoside reverse transcriptase inhibitors (NRTIs), 6.9% (95% CI 3.2-14.2) for non- nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.2% (95% CI 0.2-6.2) for protease inhibitors. Three (3.4% 95% CI 0.8-10.1) persons had dual-class NRTI/NNRTI resistance. Predominant TDR mutations in the reverse transcriptase included K103N/S (4.6%) and M184V (2.3%); only M46I/L (1.1%) occurred in the protease. All the eight persons were predicted to have different grades of resistance to the ARV regimens, ranging from potential low-level to high-level resistance. HIV-1 subtype distribution was heterogeneous: A (57.5%), C (6.9%), D (21.8%), G (2.3%), and circulating recombinant forms (11.5%). Only low CD4 count was associated with TDR (p = 0.0145). Our findings warrant the need for enhanced HIV-1 TDR monitoring in order to inform on population-based therapeutic guidelines and public health interventions.

Fig 1. Predicted antiretroviral (ARV) drug responses of eight persons with TDR mutations.

Drug responses were based on the Stanford HIVdb v7.0 report. The y-axis indicates the percentage number of sequences with TDR while the x-axis indicates the different ARV drug classes that were affected by the TDR mutations. Drugs that were unaffected by any particular TDR were excluded from the analyses. TDR—Transmitted Drug Resistance; PIs—Protease Inhibitors; NRTIs—Nucleoside Reverse Transcriptase Inhibitors; NNRTIs—Non-Nucleoside Reverse Transcriptase Inhibitors; ATV/r—Boosted Atazanavir; FPV/r—Boosted Fosamprenavir; IDV/r—Boosted Indinavir; LPV/r—Boosted Lopinavir; NFV—Nelfinavir; TPV/r—Boosted Tipranavir; r—Ritonavir; 3TC—Lamivudine; ABC—Abacavir; AZT—Zidovudine; D4T—Stavudine; DDI—Didanosine; FTC—Emtricitabine; TDF—Tenofovir; EFV—Efavirenz; ETR—Etravirine; NVP—Nevirapine; RPV—Rilpivirine.

Fig 2. Summary of the subtyping and intersubtyping results of the phylogenetic analyses represented by pie chart.